The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.
Taxol-resistant epithelial ovarian tumors are associated with altered expression of specific beta-tubulin isotypes.
Open accessAbstract
The treatment of advanced ovarian cancer with taxol is hindered by the development of drug resistance. The cellular target for taxol is the microtubule that is stabilized by the drug. Taxol preferentially binds to the beta subunit of tubulin of which there are six distinct isotypes in mammalian cells. We have used highly specific oligonucleotides and polymerase chain reaction to analyze expression of all six beta-tubulin genes. Human lung cancer cells (A549) were selected in 12 and 24 nM taxol resulting in cell lines that were 9- and 17-fold resistant, respectively. These cells displayed an altered ratio of classes I, II, III, and IVa beta-tubulin isotypes. Ovarian tumors, seven untreated primary and four taxol- resistant tumor-bearing ascites, displayed significant increases (P < 0.005) in classes I (3.6-fold), III (4.4-fold), and IVa (7.6-fold) isotypes in the taxol-resistant samples as compared with untreated primary ovarian tumors. The increased expression appears to be related to the resistance phenotype, as the basal levels of the class III and IVa isotypes in the untreated tumors were extremely low. This is the first report of altered expression of specific beta-tubulin genes in taxol-resistant ovarian tumors and we propose that the latter may play a role in clinical resistance to taxol.
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Cited by
Microtubules as a target for anticancer drugs
Jordan, M. A., & Wilson, L. (2004) · Nature Reviews Cancer · doi:10.1038/nrc1317 · Cited by 4,000
Microtubules and resistance to tubulin-binding agents
Kavallaris, M. (2010) · Nature Reviews Cancer · doi:10.1038/nrc2803 · Cited by 1,120
Self-citationMechanisms of Taxol resistance related to microtubules
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Self-citationPredictive factors for response to docetaxel in human breast cancers
Noguchi, S. (2006) · Cancer Science · doi:10.1111/j.1349-7006.2006.00265.x · Cited by 127
Src family kinases and paclitaxel sensitivity
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Metadata
- Authors
- Kavallaris, M., Kuo, D. Y., Burkhart, C. A., Regl, D. L., Norris, M. D., Haber, M., & Horwitz, S. B.
- Venue
- Journal of Clinical Investigation
- Published
- 1997-09-01
- Volume
- 100
- Issue
- 5
- Pages
- 1282-1293
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2125089526
- Cited by
- 601
- References
- 54
- FWCI
- 4.71
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Kavallaris, M., Kuo, D. Y., Burkhart, C. A., Regl, D. L., Norris, M. D., Haber, M., & Horwitz, S. B. (1997). Taxol-resistant epithelial ovarian tumors are associated with altered expression of specific beta-tubulin isotypes. Journal of Clinical Investigation. https://doi.org/10.1172/jci119642
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